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Zinc metalloproteinase ZmpC suppresses experimental pneumococcal meningitis by inhibiting bacterial invasion of central nervous systems

Streptococcus pneumoniae is a leading cause of bacterial meningitis. Here, we investigated whether pneumococcal paralogous zinc metalloproteases contribute to meningitis onset. Findings of codon-based phylogenetic analyses indicated 3 major clusters in the Zmp family; ZmpA, ZmpC, and ZmpB, with ZmpD...

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Autores principales: Yamaguchi, Masaya, Nakata, Masanobu, Sumioka, Ryuichi, Hirose, Yujiro, Wada, Satoshi, Akeda, Yukihiro, Sumitomo, Tomoko, Kawabata, Shigetada
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5810488/
https://www.ncbi.nlm.nih.gov/pubmed/28489958
http://dx.doi.org/10.1080/21505594.2017.1328333
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author Yamaguchi, Masaya
Nakata, Masanobu
Sumioka, Ryuichi
Hirose, Yujiro
Wada, Satoshi
Akeda, Yukihiro
Sumitomo, Tomoko
Kawabata, Shigetada
author_facet Yamaguchi, Masaya
Nakata, Masanobu
Sumioka, Ryuichi
Hirose, Yujiro
Wada, Satoshi
Akeda, Yukihiro
Sumitomo, Tomoko
Kawabata, Shigetada
author_sort Yamaguchi, Masaya
collection PubMed
description Streptococcus pneumoniae is a leading cause of bacterial meningitis. Here, we investigated whether pneumococcal paralogous zinc metalloproteases contribute to meningitis onset. Findings of codon-based phylogenetic analyses indicated 3 major clusters in the Zmp family; ZmpA, ZmpC, and ZmpB, with ZmpD as a subgroup. In vitro invasion assays of human brain microvascular endothelial cells (hBMECs) showed that deletion of the zmpC gene in S. pneumoniae strain TIGR4 significantly increased bacterial invasion into hBMECs, whereas deletion of either zmpA or zmpB had no effect. In a mouse meningitis model, the zmpC deletion mutant exhibited increased invasion of the brain and was associated with increased matrix metalloproteinase-9 in plasma and mortality as compared with the wild type. We concluded that ZmpC suppresses pneumococcal virulence by inhibiting bacterial invasion of the central nervous system. Furthermore, ZmpC illustrates the evolutional theory stating that gene duplication leads to acquisition of novel function to suppress excessive mortality.
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spelling pubmed-58104882018-02-15 Zinc metalloproteinase ZmpC suppresses experimental pneumococcal meningitis by inhibiting bacterial invasion of central nervous systems Yamaguchi, Masaya Nakata, Masanobu Sumioka, Ryuichi Hirose, Yujiro Wada, Satoshi Akeda, Yukihiro Sumitomo, Tomoko Kawabata, Shigetada Virulence Brief Report Streptococcus pneumoniae is a leading cause of bacterial meningitis. Here, we investigated whether pneumococcal paralogous zinc metalloproteases contribute to meningitis onset. Findings of codon-based phylogenetic analyses indicated 3 major clusters in the Zmp family; ZmpA, ZmpC, and ZmpB, with ZmpD as a subgroup. In vitro invasion assays of human brain microvascular endothelial cells (hBMECs) showed that deletion of the zmpC gene in S. pneumoniae strain TIGR4 significantly increased bacterial invasion into hBMECs, whereas deletion of either zmpA or zmpB had no effect. In a mouse meningitis model, the zmpC deletion mutant exhibited increased invasion of the brain and was associated with increased matrix metalloproteinase-9 in plasma and mortality as compared with the wild type. We concluded that ZmpC suppresses pneumococcal virulence by inhibiting bacterial invasion of the central nervous system. Furthermore, ZmpC illustrates the evolutional theory stating that gene duplication leads to acquisition of novel function to suppress excessive mortality. Taylor & Francis 2017-06-05 /pmc/articles/PMC5810488/ /pubmed/28489958 http://dx.doi.org/10.1080/21505594.2017.1328333 Text en © 2017 The Author(s). Published with license by Taylor & Francis http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.
spellingShingle Brief Report
Yamaguchi, Masaya
Nakata, Masanobu
Sumioka, Ryuichi
Hirose, Yujiro
Wada, Satoshi
Akeda, Yukihiro
Sumitomo, Tomoko
Kawabata, Shigetada
Zinc metalloproteinase ZmpC suppresses experimental pneumococcal meningitis by inhibiting bacterial invasion of central nervous systems
title Zinc metalloproteinase ZmpC suppresses experimental pneumococcal meningitis by inhibiting bacterial invasion of central nervous systems
title_full Zinc metalloproteinase ZmpC suppresses experimental pneumococcal meningitis by inhibiting bacterial invasion of central nervous systems
title_fullStr Zinc metalloproteinase ZmpC suppresses experimental pneumococcal meningitis by inhibiting bacterial invasion of central nervous systems
title_full_unstemmed Zinc metalloproteinase ZmpC suppresses experimental pneumococcal meningitis by inhibiting bacterial invasion of central nervous systems
title_short Zinc metalloproteinase ZmpC suppresses experimental pneumococcal meningitis by inhibiting bacterial invasion of central nervous systems
title_sort zinc metalloproteinase zmpc suppresses experimental pneumococcal meningitis by inhibiting bacterial invasion of central nervous systems
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5810488/
https://www.ncbi.nlm.nih.gov/pubmed/28489958
http://dx.doi.org/10.1080/21505594.2017.1328333
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